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目的:探讨丁酸钠在活体新生SD大鼠肠屏障功能中的保护作用，建立丁酸钠对活体肠黏膜作用的量效关系。方法:将出生后9 d龄的新生SD大鼠按照随机数字表法分为5组，其中4组使用丁酸钠(sodium butyrate，NaB)，浓度分别为20 mmol/L、40 mmol/L、80 mmol/L、160 mmol/L等4组，对照组使用0.9%生理盐水；经回肠灌注不同浓度的NaB作用1 h后取回肠组织，在尤斯灌注系统(Ussing Chamber)上测定跨上皮电阻(transepithelial electrical resistance，TER)值，苏木精-伊红(HE)染色观察病理学及炎症损伤情况，实时荧光定量聚合酶链反应(RT-qPCR)法检测紧密连接蛋白(Occludin、ZO -1)的mRNA表达量，Western blot法检测Occludin、ZO -1蛋白的表达水平。结果:尤斯灌注系统测得对照组在30 min、60 min、120 min时的相对TER值(各个时间点测得的TER值除以0 min测得TER值得到的百分比值)分别为(87.36±1.88)、(85.98±0.99)、(101.03±1.47)，20 mmol/L组分别为(83.45±2.97)、(107.24±5.35)、(101.44±3.96)，40 mmol/L组分别为(126.07±3.48)、(140.54±3.64)、(100.50±4.64)，80 mmol/L组分别为(102.24±4.60)、(134.55±7.80)、(106.76±8.82)，160 mmol/L组分别为(84.80±2.97)、(78.16±2.89)、(67.11±4.07)；使用不同浓度NaB作用30 min，与对照组相比，40 mmol/L组的TER值明显增加(n P<0.05)，作用1 h时，40 mmol/L组与80 mmol/L组的TER值明显高于对照组、20 mmol/L及160 mmol/L组(n P0.05)。使用不同浓度NaB作用1 h后，根据损伤分级评分(0～5分)结果，160 mmol/L组(2.16±0.75)分，较对照组(0.33±0.51)分损伤明显(n P0.05)。40 mmol/L组及80 mmol/L组肠黏膜组织Occludin蛋白mRNA(1.80±0.31、2.13±0.90)表达量较对照组(1.01±0.21)上调，差异具有统计学意义(n P<0.05)，蛋白表达水平(0.58±0.04、0.73±0.01)较对照组(0.24±0.01)明显升高，差异具有统计学意义(n P0.05)，蛋白表达水平(1.46±0.04、1.34±0.07)较对照组(1.07±0.05)亦明显升高，差异具有统计学意义(n P0.05)，而蛋白表达水平(0.47±0.01、2.90±0.04)均高于对照组，差异具有统计学意义(n P<0.01)。n 结论:NaB对活体新生SD大鼠肠黏膜的作用具有浓度依赖性，40 mmol/L或80 mmol/L的NaB能增强肠黏膜屏障的功能，这可能与肠黏膜组织Occludin和ZO -1蛋白的表达增加有关。“,”Objective:To evaluate the effect of sodium butyrate (NaB) on the protection of intestinal barrier function and establish the effect of NaB on intestinal mucosa in neonatal rats.Methods:The 9-day-old neonatal rats were randomly divided into 5 groups. The serial concentrations of NaB were set at 20, 40, 80 and 160 mmol/L. And saline was selected as a normal control. Intestinal tissue was harvested after an ileal infusion of different concentrations of NaB for 1 hour. Transepithelial electrical resistance (TER) was measured on a Ussing chamber and pathological condition and inflammatory injuries were observed by hematoxylin-eosin stain. The expressions of tight junction proteins Occludin and ZO -1 mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR), Occludin and ZO -1 protein levels were detected by Western blot.Results:(a) The value of TER (relative to initial value %) of control group at 30/60/120 min was (87.36±1.88), (85.98±0.99), (101.03±1.47) and 20 mmol/L group (83.45±2.97), (107.24±5.35), (101.44±3.96), 40 mmol/L group (126.07±3.48), (140.54±3.64), (100.50±4.64), 80 mmol/L group (102.24±4.60), (134.55±7.80), (106.76±8.82) and 160 mmol/L group (84.80±2.97), (78.16±2.89), (67.11±4.07) respectively. After acting with different concentrations of NaB for 30 min, as compared with control group, TER value of 40 mmol/L group increased markedly (n P<0.05), At 1 h, TER value of 40/80 mmol/L group was significantly higher than those of control and 20/160 mmol/L groups (n P0.05); (b) After reacting with different concentrations of sodium butyrate for 1 h, histologic injury scores was significantly higher in 160 mmol/L group than that in control group [(2.16±0.75) vs (0.33±0.51),n P0.05); (c) 40/80 mmol/L group Occludin mRNA expression (1.80±0.31, 2.13±0.90) was higher than control group (1.01±0.21)(n P<0.05) while protein level (0.58±0.04, 0.73±0.01) also increased as compared with control group (0.24±0.01) (n P0.05). However, the level of protein (1.46±0.04, 1.34±0.07) was significantly higher than that of saline group (1.07±0.05) (n P0.05) while the protein expression levels (0.47±0.01, 2.90±0.04) were higher than that of control group (n P<0.01).n Conclusions:NaB affects on intestinal barrier function in a time/dose-dependent manner. And 40/80 mmol/L sodium butyrate enhances intestinal mucosal barrier through the up-regulations of Occludin and ZO -1.